Second‐Generation Amino Acid Furanoside Based Ligands from D‐Glucose for the Asymmetric Transfer Hydrogenation of Ketones

Abstract

AbstractA novel series of modular amino acid thioamide ligands functionalized with carbohydrates were introduced and employed in the rhodium‐catalyzed asymmetric transfer hydrogenation (ATH) of aryl alkyl ketones, including the less‐studied heteroaromatic ketones. The ligands are based on amino acid hydroxyamides (pseudodipeptides), which are the most successful ligands previously used in asymmetric hydrogen transfer reactions. High enantioselectivities [up to 99 % enantiomeric excess (ee)] were achieved in the ATH of a wide range of aryl alkyl ketones by using catalysts generated in situ from [RhCl2Cp*]2 (Cp*=C5Me5) and thioamide ligands comprising a 3‐benzyl glucofuranoside backbone and a bulky isopropyl group in the α‐amino acid moiety. Interestingly, both enantiomers of the alcohol products can readily be obtained with high enantioselectivity by simply changing the absolute configuration of the α‐amino acid. The good performance can be extended to a very challenging class of industrially interesting heteroaromatic ketones (up to 99 % ee).